What's new for 'Trypanosomatids' in PubMed

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Sent on Thursday, 2011 Jul 07
Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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PubMed Results

Items 1 - 3 of 3

1.	PLoS One. 2011;6(6):e21412. Epub 2011 Jun 23. Molecular and Cellular Characterization of an AT-Hook Protein from Leishmania. Kelly BL, Singh G, Aiyar A. Source Department of Microbiology, Immunology and Parasitology, Lousiana State University Health Sciences Center, New Orleans, Louisiana, United States of America. Abstract AT-rich DNA, and the proteins that bind it (AT-hook proteins), modulate chromosome structure and function in most eukaryotes. Unlike other trypanosomatids, the genome of Leishmania species is unusually GC-rich, and the regulation of Leishmania chromosome structure, replication, partitioning is not fully understood. Because AT-hook proteins modulate these functions in other eukaryotes, we examined whether AT-hook proteins are encoded in the Leishmania genome, to test their potential functions. Several Leishmania ORFs predicted to be AT-hook proteins were identified using in silico approaches based on sequences shared between eukaryotic AT-hook proteins. We have used biochemical, molecular and cellular techniques to characterize the L. amazonensis ortholog of the L. major protein LmjF06.0720, a potential AT-hook protein that is highly conserved in Leishmania species. Using a novel fusion between the AT-hook domain encoded by LmjF06.0720 and a herpesviral protein, we have demonstrated that LmjF06.0720 functions as an AT-hook protein in mammalian cells. Further, as observed for mammalian and viral AT-hook proteins, the AT-hook domains of LmjF06.0720 bind specific regions of condensed mammalian metaphase chromosomes, and support the licensed replication of DNA in mammalian cells. LmjF06.0720 is nuclear in Leishmania, and this localization is disrupted upon exposure to drugs that displace AT-hook proteins from AT-rich DNA. Coincidentally, these drugs dramatically alter the cellular physiology of Leishmania promastigotes. Finally, we have devised a novel peptido-mimetic agent derived from the sequence of LmjF06.0720 that blocks the proliferation of Leishmania promastigotes, and lowers amastigote parasitic burden in infected macrophages. Our results indicate that AT-hook proteins are critical for the normal biology of Leishmania. In addition, we have described a simple technique to examine the function of Leishmania chromatin-binding proteins in a eukaryotic context amenable to studying chromosome structure and function. Lastly, we demonstrate the therapeutic potential of compounds directed against AT-hook proteins in Leishmania.
	PMID: 21731738 [PubMed - as supplied by publisher]

2.	BMC Evol Biol. 2011 Jul 5;11(1):193. [Epub ahead of print] Protein functional links in Trypanosoma brucei, identified by gene fusion analysis. Dimitriadis D, Koumandou VL, Trimpalis P, Kossida S. Abstract ABSTRACT: BACKGROUND: Domain or gene fusion analysis is a bioinformatics method for detecting gene fusions in one organism by comparing its genome to that of other organisms. The occurrence of gene fusions suggests that the two original genes that participated in the fusion are functionally linked, i.e. their gene products interact either as part of a multi-subunit protein complex, or in a metabolic pathway. Gene fusion analysis has been used to identify protein functional links in prokaryotes as well as in eukaryotic model organisms, such as yeast and Drosophila. RESULTS: In this study we have extended this approach to include a number of recently sequenced protists, four of which are pathogenic, to identify fusion linked proteins in Trypanosoma brucei, the causative agent of African sleeping sickness. We have also examined the evolution of the gene fusion events identified, to determine whether they can be attributed to fusion or fission, by looking at the conservation of the fused genes and of the individual component genes across the major eukaryotic and prokaryotic lineages. We find relatively limited occurrence of gene fusions/fissions within the protist lineages examined. Our results point to two trypanosome-specific gene fissions, which have recently been experimentally confirmed, one fusion involving proteins involved in the same metabolic pathway, as well as two novel putative functional links between fusion-linked protein pairs. CONCLUSIONS: This is the first study of protein functional links in T. brucei identified by gene fusion analysis. We have used strict threshold and only discuss results which are highly likely to be genuine and which either have already been or can be experimentally verified. We discuss the possible impact of the identification of these novel putative protein-protein interactions, to the development of new trypanosome therapeutic drugs.
	PMID: 21729286 [PubMed - as supplied by publisher]

3.	Parasite Immunol. 2011 Jul 5. doi: 10.1111/j.1365-3024.2011.01315.x. [Epub ahead of print] High Concentration of Adenosine in Human Visceral Leishmaniasis: Despite Increased ADA and Decreased CD73. Rai AK, Thakur CP, Velpandian T, Sharma SK, Ghosh B, Mitra DK. Source Department of Transplant Immunology & Immunogenetics, All India Institute of Medical Sciences, New Delhi-110029, India Balaji Utthan Sansthan, Fraser Road, Patna, Bihar, India Department of Ocular Pharmacology, R.P. Ophthalmology Center, All India Institute of Medical Sciences, New Delhi-110029, India Department of Medicine, All India Institute of Medical Sciences, New Delhi-110029, India Division of Molecular and Clinical Immunology, Institute of Genomics and Integrated Biology, New Delhi, India. Abstract Absence of an effective Th-1 response has been demonstrated as a major cause for the disease pathology among visceral leishmaniasis (VL) patients. Defining strategies to prevent the development of Th-2 response and/or initiate/activate effective Th-1 response may be of help to reduce the growing incidence of drug unresponsiveness. Adenosine considered as an endogenous anti-inflammatory agent, is generated in injured/inflamed tissues by the enzymatic catabolism of adenosine tri-phosphate (ATP) and it suppresses inflammatory responses of essentially all immune cells. The extracellular adenosine producing pathway comprises two major enzymes CD39 (ATPâ†'ADPâ†'AMP) and CD73 (AMPâ†'Adenosine). In contrast, the adenosine degrading pathway contains only one major enzyme adenosine deaminase (ADA). Our study shows high concentration of adenosine in diseased condition, varying expression of enzyme involved in adenosine producing (CD73â†") and degrading (ADAâ†') pathways. These are less studied in infections like VL but are very important in terms of endogenous regulation of immune response among patients. Copyright © 2011 Blackwell Publishing Ltd.
	PMID: 21729107 [PubMed - as supplied by publisher]